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Bypass is often achieved by supplementation with the product of the enzyme. However, supplementation cannot bypass loss of essential genes such as those encoding enzymes of DNA or RNA synthesis. To study proteins encoded by essential genes that cannot be bypassed, the mutations must be conditional in nature. The mutant cells must be able to grow under a permissive condition, but fail to grow under a different condition, the nonpermissive condition. Several methods have been developed to obtain conditional mutations in essential genes. Mutations that result in proteins abnormally sensitive to high temperatures are called temperature\u2010sensitive (Ts) mutants and are a widely used type of conditional mutation. An alternative to Ts mutants is the \u201cdegron\u201d system to target proteins for destruction by cellular proteases. Approaches to conditionally control the functions of proteins encoded by essential genes, plus the advantages and disadvantages of these and other approaches, will be considered.<\/jats:p>","DOI":"10.1002\/prot.70039","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T04:14:54Z","timestamp":1755317694000},"page":"463-476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Approaches to Study Proteins Encoded by Essential Genes"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7064-312X","authenticated-orcid":false,"given":"John E.","family":"Cronan","sequence":"first","affiliation":[{"name":"Department of Microbiology University of Illinois  Urbana Illinois USA"},{"name":"Department of Biochemistry University of Illinois  Urbana Illinois 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